The delivery of drugs to a patient is conventionally performed in a number of different ways. For example, intravenous delivery is by injection directly into a blood vessel; intraperitoneal delivery is by injection into the peritoneum; subcutaneous delivery is under the skin; intramuscular delivery is into a muscle; and oral delivery is through the mouth. The stratum corneum is a tough, scaly layer made of dead cell tissue that extends around 10-20 microns from the skin surface and has no blood supply. Because of the density of this layer of cells, moving compounds across the skin, either into or out of the body, can be very difficult.
Current techniques for delivering local pharmaceuticals through the skin include methods that use needles or other skin piercing devices and methods that do not use such devices. Invasive procedures, such as use of needles or lances, can effectively overcome the barrier function of the stratum corneum. However, these methods suffer from several major disadvantages, including pain, local skin damage, bleeding, risk of infection at the injection site, and creation of contaminated needles or lances. These methods also usually require a trained administrator and are not suitable for repeated, long-term, or controlled use.
MNs (“MNs”) are an alternative technique used to permeabilize the stratum corneum (hereinafter “SC”) barrier and increase the number of drugs that can be delivered transdermally. The MNs are similar to larger conventional medical needles, so that drug compounds may be delivered through the shaft and into the skin. The skin is a self-regulatory organ and employs different methods for recovery after assault. Skin wound healing consists of multiple phases, inflammatory response being the first step. Transdermal patch occlusion helps to delay the recovery process. However, micropores created by MNs begin to close between 48-72 hours for the specific MN geometry.
As such, a need currently exists for a transdermal MN device that can easily deliver a drug compound for a 7-day period. Therefore, in order to develop a 7-day transdermal drug delivery system, pore lifetime enhancement techniques need to be employed in order to allow for continued skin permeation. Lipid biosynthesis inhibitors such as HMG-CoA reductase inhibitors can be used to delay the normal healing process thus enhancing micropore lifetime and pore viability. By combining the transdermal drug with a lipid biosynthesis inhibitor such as fluvastatin (a HMG CoA reductase inhibitor) (“FLU”) or other compound, which inhibits the biosynthesis of cholesterol, a lipid component of skin, the skin recovery process can be improved. This skin recovery inhibition helps to extend and maintain the lifetime of the skin micropores and allow sustained delivery of a drug transdermally.